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New Bedford, MA, United States

Stein T.D.,VA Boston Healthcare System | Stein T.D.,Boston University | Alvarez V.E.,Bedford Medical Center | Alvarez V.E.,Boston University | And 2 more authors.
Alzheimer's Research and Therapy

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in sport and military service. In most instances, the clinical symptoms of the disease begin after a long period of latency ranging from several years to several decades. The initial symptoms are typically insidious, consisting of irritability, impulsivity, aggression, depression, short-term memory loss and heightened suicidality. The symptoms progress slowly over decades to include cognitive deficits and dementia. The pathology of CTE is characterized by the accumulation of phosphorylated tau protein in neurons and astrocytes in a pattern that is unique from other tauopathies, including Alzheimer's disease. The hyperphosphorylated tau abnormalities begin focally, as perivascular neurofibrillary tangles and neurites at the depths of the cerebral sulci, and then spread to involve superficial layers of adjacent cortex before becoming a widespread degeneration affecting medial temporal lobe structures, diencephalon and brainstem. Most instances of CTE (>85% of cases) show abnormal accumulations of phosphorylated 43 kDa TAR DNA binding protein that are partially colocalized with phosphorylated tau protein. As CTE is characterized pathologically by frontal and temporal lobe atrophy, by abnormal deposits of phosphorylated tau and by 43 kDa TAR DNA binding protein and is associated clinically with behavioral and personality changes, as well as cognitive impairments, CTE is increasingly categorized as an acquired frontotemporal lobar degeneration. Currently, some of the greatest challenges are that CTE cannot be diagnosed during life and the incidence and prevalence of the disorder remain uncertain. Furthermore, the contribution of age, gender, genetics, stress, alcohol and substance abuse to the development of CTE remains to be determined. © 2014 BioMed Central Ltd. Source

Bird S.S.,Harvard University | Sheldon D.P.,Harvard University | Gathungu R.M.,Northeastern University | Vouros P.,Northeastern University | And 3 more authors.
Analytical Chemistry

Liquid chromatography (LC) separation combined with electrochemical coulometric array detection (EC) is a sensitive, reproducible, and robust technique that can detect hundreds of redox-active metabolites down to the level of femtograms on column, making it ideal for metabolomics profiling. EC detection cannot, however, structurally characterize unknown metabolites that comprise these profiles. Several aspects of LC-EC methods prevent a direct transfer to other structurally informative analytical methods, such as LC-MS and NMR. These include system limits of detection, buffer requirements, and detection mechanisms. To address these limitations, we developed a workflow based on the concentration of plasma, metabolite extraction, and offline LC-UV fractionation. Pooled human plasma was used to provide sufficient material necessary for multiple sample concentrations and platform analyses. Offline parallel LC-EC and LC-MS methods were established that correlated standard metabolites between the LC-EC profiling method and the mass spectrometer. Peak retention times (RT) from the LC-MS and LC-EC system were linearly related (r2 = 0.99); thus, LC-MS RTs could be directly predicted from the LC-EC signals. Subsequent offline microcoil-NMR analysis of these collected fractions was used to confirm LC-MS characterizations by providing complementary, structural data. This work provides a validated workflow that is transferrable across multiple platforms and provides the unambiguous structural identifications necessary to move primary mathematically driven LC-EC biomarker discovery into biological and clinical utility. © 2012 American Chemical Society. Source

Laska K.M.,Bedford Medical Center | Wampold B.E.,University of Wisconsin - Madison | Wampold B.E.,Modum Bad Psychiatric Center

Recently, we (Laska, Gurman,&Wampold, 2014, pp. 467-481) discussed the implications of taking a common factor approach for practice and policy. In this response to the commentary on our article, we reiterate 10 things that need to be remembered about common factor theory. © 2014 American Psychological Association. Source

Laska K.M.,Bedford Medical Center | Gurman A.S.,Northwestern University | Gurman A.S.,University of Wisconsin - Madison | Wampold B.E.,University of Wisconsin - Madison

In this article, we examine the science and policy implications of the common factors perspective (CF; Frank&Frank, 1993; Wampold, 2007). As the empirically supported treatment (EST) approach, grounded in randomized controlled trials (RCTs), is the received view (see Baker, McFall,&Shoham, 2008; McHugh&Barlow, 2012), we make the case for the CF perspective as an additional evidencebased approach for understanding how therapy works, but also as a basis for improving the quality of mental health services. Finally, we argue that it is time to integrate the 2 perspectives, and we challenge the field to do so. © 2014 American Psychological Association. Source

Singh J.A.,University of Alabama at Birmingham | Houston T.K.,Bedford Medical Center | Ponce B.A.,University of Alabama at Birmingham | Maddox G.,University of Alabama at Birmingham | And 6 more authors.
Arthritis Care and Research

Objective. To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR). Methods. We used data from the national Veterans Affairs Surgical Quality Improvement Program to examine the association of smoking status at surgery with 30-day postoperative complication rates (including surgical site and other infections, pneumonia, stroke, myocardial infarction, mortality, and other complications) in veterans undergoing primary elective THR or TKR. Multilevel multivariable-adjusted logistic regression models, adjusted for age, race/ethnicity, work relative value units, American Society of Anesthesiology classification, and year of surgery, with additional adjustment for wound classification for surgical site infections, were used. Results. A total of 33,336 patients, 95% men and 80% white with a mean age of 64 years, underwent elective primary THR/TKR between October 2001 and September 2008. Fifty-seven percent never smoked, 19% were prior smokers, and 24% were current smokers. Current smokers undergoing THR/TKR were significantly more likely than never smokers to have surgical site infections (odds ratio [OR] 1.41, 95% CI 1.16-1.72), pneumonia (OR 1.53, 95% CI 1.10-2.14), stroke (OR 2.61, 95% CI 1.26-5.41), and 1-year mortality (OR 1.63, 95% CI 1.31-2.02). Prior smokers were significantly more likely than nonsmokers to have pneumonia, (OR 1.34, 95% CI 1.00-1.80), stroke (OR 2.14, 95% CI 1.12-4.10), and urinary tract infection (OR 1.26, 95% CI 1.02-1.55). Conclusion. Current smoking at the time of elective THR or TKR is associated with increased postarthroplasty complications, especially surgical site infections and pneumonia. Preoperative smoking cessation programs should be considered in patients undergoing elective THR or TKR. © 2011. American College of Rheumatology. Source

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